Synthesis and antimicrobial activity of novel 1-[3-(1,8-naphthyridin-2-yl)phenyl]-3-arylurea derivatives

Article abstract of DOI:10.14233/ajchem.2018.20972

2-Aminonicotinaldehyde (1) and 1-(3-nitrophenyl)ethanone (2) react each other in presence of piperidine to form 2-(3-nitrophenyl)-1,8-naphthyridine (3). Compound 3 on reduction with hydrazine hydrate offered 3-(1,8-naphthyridin-2-yl)aniline (4), which on

Full text of DOI:10.14233/ajchem.2018.20972

Asian Journal of Chemistry; Vol. 30, No. 4 (2018), 771-774
A
SIAN
J
OURNAL OF HEMISTRY
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https://doi.org/10.14233/ajchem.2018.20972
Synthesis and Antimicrobial Activity of Novel
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-arylurea Derivatives
1
1
1
2
1,*
G. VIJAYA BHASKER , G.V. SATYANARAYANA , A. LATHA , E. LAXMINARAYANA and M. THIRUMALA CHARY
1Department of Chemistry, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad-500 085, India
2Department of Science & Humanities, Sreenidhi Institute of Science & Technology. Yamnampet, Ghatkesar, Hyderabad-501 301, India
*Corresponding author: E-mail: mtcharya@yahoo.com
Received: 14 August 2017;
Accepted: 22 September 2017;
Published online: 28 February 2018;
AJC-18781
2-Aminonicotinaldehyde (1) and 1-(3-nitrophenyl)ethanone (2) react each other in presence of piperidine to form 2-(3-nitrophenyl)-1,8-
naphthyridine (3). Compound 3 on reduction with hydrazine hydrate offered 3-(1,8-naphthyridin-2-yl)aniline (4), which on condensation
with different arylcarbamates results in formation of 1-[3-(1,8-naphthyridin-2-yl)phenyl]-3-arylurea derivatives (6a-q). The structures of
all the compounds are confirmed by IR, NMR and mass spectral data. Further the newly synthesized compounds were evaluated for
antimicrobial activity. The results obtained revealed that the tested compounds possess inhibitory effect on the growth of bacterial cells.
Keywords: Naphthyridine derivatives, Piperidine, Urea, Antimicrobial activity.
and only diagnostic and/or intense peaks are reported.1H NMR
INTRODUCTION
spectra were recorded in DMSO-d6 with a Varian Mercury
Naphthyridine derivatives have received significant atten-
plus 400 MHz instrument. Signals due to residual protonated
solvent (1H NMR) served as the internal standard. All the
tion due to their exceptionally broad spectrum of biological
activity. Many researchers focus on synthesis of these mole-
chemical shifts were presented in δ (ppm) using TMS as an
internal standard. The 1H NMR chemical shifts and coupling
cules as they possess wide range of biological activity. For
example, finding of the grown-up quinolinones, namely nalidixic
constants were determined assuming first-order behaviour.
acid, which has been used for the treating of a wide variety of
Mass spectra were recorded with a PE Sciex model API 3000
diseases, led to the production of many 1,8-naphthyridin-5-
instrument. All the reactions were carried out under argon
one derivatives with the strong antibacterial enoxacin [1,2].
atmosphere.
Many of the naphthyridines have shown bacterial, fungicidal
Biological assay: The synthesized compounds were
and carcinogenic activities [3-6]. In recent past, study on deri-
dissolved in dimethyl sulphoxide at 30 µg/µL concentration
vatives of 1,8-naphthyridine has been concentrated as these
(standard antibacterial drug, ampicilline was used as the refe-
compounds show a broad spectrum of biological activities
rence antibiotic) and tested against Gram-negative strains of
[7-15].A very few reports available on synthesis of urea deriva-
tive on naphthyridine. We have synthesized these compounds
Escherichia coli, Klebsiella pneumonia and Gram-positive
strains of Staphylococcus aureus and Bacillus subtilis using
by using carbamates. In continuation of our earlier reports
agar well diffusion method.Activities were determined by zones
[16-24] on synthesis of naphthyridine derivatives, we herein
showing complete inhibition (mm). Growth inhibition was
report a novel approach to synthesize 1-[3-(1,8-naphthyridin-
calculated with reference to positive control. All the samples
2-yl)phenyl]-3-arylurea derivatives.
were taken in triplicates.
Synthesis of 2-(3-Nitrophenyl)-1,8-naphthyridine (3):
EXPERIMENTAL
To a stirred solution of 2-aminonicotinaldehyde (1 g, 8.18
All the chemical used were obtained either from Fluka or
Merck and were of analytical grade. Thin-layer chromato-
graphy (TLC) was performed on MerckAL silica gel 60 F254
plates and envisioned in UV light. IR spectra were recorded as
KBr pellet with a Perkin-Elmer spectrum GX FTIR instrument
mmol) in ethyl alcohol (20 mL) was added 1-(3-nitrophenyl)-
ethanone (1.48 g, 9.00 mmol) and piperidine (2.09 g, 24.56
mmol) at room temperature and refluxed for 16 h. After
completion of the reaction (monitored by TLC), the mixture
was concentrated under reduced pressure and the crude product

772 Bhasker et al.
Asian J. Chem.
washed with 10 % dichloromethane in diethyl ether to afford
2-(3-nitrophenyl)-1,8-naphthyridine (3).
δ 159.7, 155.4, 153.7, 149.1, 138.8, 138.2, 137.1, 129.3, 121.8,
121.4, 119.5, 115.8, 115.2, 112.7; ESI-MS: m/z, 222.19 (M+1).
Synthesis of phenyl phenylcarbamate derivatives (5a-q):
To a stirred solution of anilines (3.29 mmol) in dichloromethane
(6 mL) was added triethylamine (9.89 mmol) at room tempe-
rature and stirred at room temperature for 10 min and added
aryl chloro formate (4.93 mmol) at 0 °C and stirred at room
temperature for 2 h. The reaction mixture was concentrated
under reduced pressure and the crude material washed with
10 % diethyl ether in pentane to afford the pure compounds.
Without further purification used for next step. Yields of the
products varied between 65 to 85 %.
Preparation of novel 1-[3-(1,8-naphthyridin-2-yl)phenyl]-
3-phenylurea derivatives (6a-6q): To a stirred solution of
3-(1,8-naphthyridin-2-yl)aniline (100 mg, 0.40 mmol) in dimethyl
formamide (2 mL) was added corresponding arylcarbamates
(1.2 mmol) and tri ethyl amine (2.0 mmol) at room temperature
and stirred at 100 °C for 3 h. The reaction mixture was poured
into water (4 mL) and extracted with ethyl acetate (3 × 5 mL).
The combined organic layers were washed with water (5 mL)
followed by brine solution (5 mL), dried over anhydrous sodium
sulfate, filtered and concentrated under reduced pressure, to
obtain crude material was washed with methanol to afford the
pure compounds. Yields of the products varied between 50 to
80 % (Scheme-I).
Off-white solid;Yield: 65 %; m.p: 220-223 °C; 1H NMR
(500 MHz, DMSO-d6): δ 9.16-9.14 (m, 2H), 8.77 (d, J = 7.5
Hz, 1H), 8.66 (d, J = 8.5 Hz, 1H), 8.54 (dd, J = 2.0, 8.0 Hz,
1H), 8.44 (d, J = 8.5 Hz, 1H), 8.39 (dd, J = 2.0, 8.0 Hz, 1H),
7.89 (t, J = 8.0 Hz, 1H), 7.68 (dd, J = 4.0, 8.5 Hz, 1H); ESI-
MS: m/z, 252.0 (M+1).
Synthesis of 3-(1,8-naphthyridin-2-yl)aniline (4): To a
stirred suspension of raney nickel (0.92 g, 10.75 mmol) in
ethyl alcohol (20 mL) was added 2-(3-nitrophenyl)-1,8-naph-
thyridine (1 g, 3.58 mmol) and hydrazine hydrate (80 %) (0.54
g, 10.75 mmol) at room temperature and stirred at room tempe-
rature for 3 h. After completion of the reaction (monitored by
TLC), the mixture was filtered through celite pad and the filtrate
was concentrated under reduced pressure. The crude product
was washed with 10 % dichloromethane in diethyl ether to
afford 3-(1,8-naphthyridin-2-yl)aniline (4).
IR (KBr, νmax, cm–1): 3413.58, 3318.2, 3215.0, 3028.2,
1600.60, 1323.72, 846.62. Off-white solid;Yield: 73 %; m.p:
172-176 °C; 1H NMR (500 MHz, DMSO-d6): δ 9.07 (dd, J =
2.0, 4.0 Hz, 1H), 8.49 (d, J = 9.0 Hz, 1H), 8.44 (dd, J = 1.5,
8.0 Hz, 1H), 8.11 (d, J = 8.5 Hz, 1H), 7.60-7.57 (m, 2H), 7.40
(d, J = 7.5 Hz, 1H), 7.21 (t, J = 8.0 Hz, 1H), 6.74 (dd, J = 1.5,
7.5 Hz, 1H), 5.32 (s, 2H); 13C NMR (75.47 MHz, DMSO-d6):
O
R
O
a
b
5a-5q
NH NH
NH2
NO2
N
N
N
N
N
N
d
N
NH2
NO2
HN
O
4
3
1
2
6a-6q
O
NH2
c
O
R
R
a- q
5a-5q
R =
H2N
H2N
Cl
Cl
H2N
Cl
O
H2N
CN
H2N
N
H2N
O
Cl
N
c
a
f
e
b
d
H2N
Cl
H2N
F
H2N
CF3
CN
H2N
H2N
H2N
Cl
O
g
k
l
Cl
h
i
j
H2N
Cl
H2N
N
H2N
H2N
H2N
Cl
N
N
n
CN
o
m
q
p
Scheme-I: Synthesis of novel 1-[3-(1,8-naphthyridin-2-yl)phenyl]-3-arylurea derivatives (6a-6q). Reagents and conditions: (a) piperidine,
ethanol, 70 °C, 16 h; (b) Raney Ni, NH2NH2·H2O, ethanol, room temperature, 3 h; (c) triethyl amine, DCM, 0 °C-RT, 2 h; (d)
triethyl amine, DMF, 100 °C, 2 h

Vol. 30, No. 4 (2018)
Synthesis of Novel 1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-arylurea Derivatives 773
Spectral data
(s, 1H), 9.16 (s, 1H), 9.10 (d, J = 2.5 Hz, 1H), 8.56 (d, J = 8.5
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(2-chloro-5-
methoxyphenyl)urea (6a): IR (KBr, νmax, cm–1): 3296.22,
3054.46, 1709.44, 1533.36, 1209.47. Yellow solid; Yield: 75
%; m.p: 262-265 °C; 1H NMR (300 MHz, DMSO-d6): δ 9.80
(s, 1H), 9.11 (s, 1H), 8.57 (d, J = 8.4 Hz, 1H), 8.50-8.48 (m,
2H), 8.31 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.94-7.91 (m, 2H),
7.68-7.66 (m, 2H), 7.51 (t, J = 7.8 Hz, 1H), 7.36 (d, J = 8.7
Hz, 1H), 6.63 (dd, J = 2.1, 8.7 Hz, 1H), 3.76 (s, 3H); ESI-MS:
m/z, 405.3 (M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(3-cyano-
phenyl)urea (6b): IR (KBr, νmax, cm–1): 3333.9, 3020.25,
1562.1, 1200.4, 789.960.Yellow solid;Yield: 80 %; m.p: 146-
149 °C; 1H NMR (300 MHz, DMSO-d6): δ 9.14 (s, 1H), 9.11
(brs, 1H), 9.08 (s, 1H), 8.57 (d, J = 8.4 Hz, 1H), 8.51-8.49 (m,
1H), 8.48 (d, J = 1.5 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 8.03 (t,
J = 1.8 Hz, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.72 (d, J = 8.4 Hz,
1H), 7.65-7.61 (m, 2H), 7.51 (t, J = 7.2 Hz, 1H), 7.45-7.42
(m, 2H); 13C NMR (75.47 MHz, DMSO-d6): δ 159.0, 155.4,
154.0, 152.6, 140.6, 140.2, 140.0, 138.9, 137.4, 130.2, 129.5,
125.5, 123.2, 123.1, 122.7, 122.2, 121.2, 121.0, 120.4, 119.6,
118.9, 117.6; ESI-MS: m/z, 366.1 (M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(3-methylpyrazin-
2-yl)urea (6c): IR (KBr, νmax, cm–1): 3256.9, 3028.6, 1697.2,
1483.2, 1254.5, 752.1. White solid; Yield: 65 %; m.p: 282-
286 °C; 1H NMR (500 MHz, DMSO-d6): δ 9.86 (s, 1H), 9.59
(s, 1H), 9.12 (dd, J = 2.0, 2.0 Hz, 1H), 8.77 (s, 1H), 8.58 (d, J =
8.5 Hz, 1H), 8.52-8.49 (m, 3H), 8.19 (d, J = 8.5 Hz, 1H), 7.94-
7.90 (m, 1H), 7.59-7.52 (m, 1H), 7.63 (d, J = 4.0 Hz, 1H), 7.54
(t, J = 8.0 Hz, 1H), 2.46 (s, 3H); ESI-MS: m/z, 357 (M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-[3-(benzyloxy)-
phenyl]urea (6d): IR (KBr, νmax, cm–1): 3300.7, 3062.68,
1563.2, 1238.1, 793.8. Off-white solid;Yield: 70 %; m.p: 200-
202 °C; 1H NMR (300 MHz, DMSO-d6): δ 9.11 (s, 1H), 8.88
(s, 1H), 8.58 (s, 1H), 8.55 (d, J = 4.5 Hz, 1H), 8.51 (s, 1H),
8.47 (d, J = 3.6 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.87 (d, J =
7.5 Hz, 1H), 7.65-7.60 (m, 2H), 7.50-7.32 (m, 9H), 6.96 (d, J
= 9.0 Hz, 1H), 5.07 (s, 2H); ESI-MS: m/z, 447 (M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(3,4-dichloro-
phenyl)urea (6e): Off-white solid; Yield: 65 %; m.p: 150-
152 °C; 1H NMR (300 MHz, DMSO-d6): δ 9.10-9.05 (m, 3H),
8.57 (d, J = 8.4 Hz, 1H), 8.58-8.48 (m, 2H), 8.22 (d, J = 8.1
Hz, 1H), 7.93-7.91 (m, 2H), 7.65-7.60 (m, 2H), 7.54-7.47 (m,
2H), 7.38 (dd, J = 8.7, 1.8 Hz, 1H); 13C NMR (75.47 MHz,
DMSO-d6): δ 159.0, 155.4, 154.0, 152.5, 140.0, 139.9, 138.9,
137.4, 131.1, 130.6, 129.5, 123.3, 122.2, 121.7, 121.6, 120.4,
119.7, 119.6, 119.5, 118.5, 117.6; ESI-MS: m/z, 409 (M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(4-chloro-3-
methylphenyl)urea (6f): Light brown solid;Yield: 60 %; m.p:
245-249 °C; 1H NMR (500 MHz, DMSO-d6): δ 9.11 (dd, J =
4.0, 2.0 Hz, 1H), 8.97 (s, 1H), 8.77 (s, 1H), 8.74 (s, 1H), 8.56
(d, J = 8.5 Hz, 1H), 8.51-8.48 (m, 1H), 8.21 (d, J = 8.5 Hz,
1H), 7.89 (d, J = 7.5 Hz, 1H), 7.64-7.59 (m, 1H), 7.52-7.47
(m, 1H), 7.44 (s, 1H), 7.34 (dd, J = 8.5, 2.0 Hz, 1H), 7.31-
7.28 (m, 2H), 2.31 (s, 3H); ESI-MS: m/z, 389 (M+1).
Hz, 1H), 8.48 (d, J = 7.5 Hz, 1H), 8.21 (dd, J = 8.5, 1.0 Hz,
1H), 7.95-7.87 (m, 1H), 7.66-7.60 (m, 2H), 7.58 (d, J = 1.5
Hz, 1H), 7.49 (dt, J = 3.0, 3.5, 3.5 Hz, 1H), 7.19-7.11 (m,
1H), 6.97-6.92 (m, 1H); ESI-MS: m/z, 407 (M-1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-[4-cyano-3-
(trifluoromethyl)phenyl]urea (6h): Light brown solid;Yield:
1
60 %; m.p: 180-183 °C; H NMR (500 MHz, DMSO-d6): δ
9.64 (s, 1H), 9.31 (s, 1H), 9.11 (dd, J = 3.5, 1.5 Hz, 1H), 8.58
(d, J = 9.0 Hz, 1H), 8.52 (t, J = 1.5 Hz, 1H), 8.50 (dd, J = 8.0,
1.5 Hz, 1H), 8.26 (d, J = 1.5 Hz, 1H), 8.23 (d, J = 8.5 Hz, 1H),
8.05 (d, J = 8.5 Hz, 1H), 7.96 (d, J = 7.5 Hz, 1H), 7.83 (dd, J
= 8.0, 1.0 Hz, 1H), 7.65-7.62 (m, 2H), 7.53 (t, J = 8.0 Hz,
1H); ESI-MS: m/z, 434 (M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-[4-(benzyloxy)-
phenyl]urea (6i): Light brown solid; Yield: 72 %; m.p: 172-
177 °C; 1H NMR (500 MHz, DMSO-d6): δ 9.11 (dd, J = 4.0,
1.5 Hz, 1H), 8.87 (brs, 1H), 8.57-8.46 (m, 1H), 8.38 (brs, 1H),
8.21 (d, J = 8.5 Hz, 1H), 7.87 (d, J = 7.5 Hz, 1H), 7.63 (dd, J
= 8.5, 4.5 Hz, 1H), 7.60 (brs, 1H), 7.49-7.30 (m, 9H), 6.97-
6.92 (m, 3H), 5.05 (s, 2H); ESI-MS: m/z, 447 (M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(3-methyl-[1,1'-
biphenyl]-2-yl)urea (6j): Off-white solid; Yield: 66 %; m.p:
225-227 °C; 1H NMR (400 MHz, DMSO-d6): δ 9.09 (dd, J =
4.0, 1.6 Hz, 1H), 8.87 (bs, 1H), 8.55 (d, J = 8.4 Hz, 1H), 8.47
(dd, J = 8.0, 1.6 Hz, 1H), 8.35 (bs, 1H), 8.29 (s, 1H), 8.16 (d,
J = 8.4 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.63-7.60 (m, 2H),
7.55 (d, J = 8.0 Hz, 1H), 7.45-7.38 (m, 4H), 7.34-7.25 (m, 3H),
7.17(dd, J=7.2, 1.6Hz, 1H), 2.31(s, 3H);ESI-MS:m/z, 431(M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(4-chloro-3-
fluorophenyl)urea (6k): White solid;Yield: 72 %; m.p: 230-
235 °C; 1H NMR (500 MHz, DMSO-d6): δ 9.11 (dd, J = 2.0,
2.0 Hz, 1H), 9.06 (s, 1H), 8.95 (s, 1H), 8.57 (d, J = 8.5 Hz,
1H), 8.51 (d, J = 2.0 Hz, 1H), 8.49 (t, J = 2.0 Hz, 1H), 8.22 (d,
J = 9.0 Hz, 1H), 7.92-7.91 (m, 1H), 7.87-7.85 (m, 1H), 7.64
(d, J = 4.5 Hz, 1H), 7.63-7.61 (m, 1H), 7.50 (t, J = 8.0 Hz,
1H), 7.36-7.34 (m, 2H); 13C NMR (75.47 MHz, DMSO-d6): δ
159.0, 155.4, 154.1, 152.7, 140.1, 138.9, 137.4, 137.0, 136.9,
129.5, 122.3, 121.8, 121.5, 120.4, 119.8, 119.7, 118.8, 118.7,
117.6, 117.0, 116.8; ESI-MS: m/z, 393 (M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-phenylurea
1
(6l): Light brown solid; Yield: 66 %; m.p: 218-220 °C; H
NMR (500 MHz, DMSO-d6): δ 9.11 (dd, J = 2.0, 2.0 Hz, 1H),
8.94 (s, 1H), 8.71 (s, 1H), 8.57 (d, J = 8.5 Hz, 1H), 8.50 (d, J
= 2.0 Hz, 1H), 8.49-8.48 (m, 1H), 8.21 (d, J = 8.0 Hz, 1H),
7.89 (d, J = 8.0 Hz, 1H), 7.64-7.61 (m, 2H), 7.51-7.44 (m, 3H),
7.31-7.26 (m, 2H), 7.00-6.95 (m, 1H); ESI-MS: m/z, 341 (M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(2-chloropyridin-
4-yl)urea (6m): Light brown solid; Yield: 76 %; m.p: 180-
185 °C; 1H NMR (500 MHz, DMSO-d6): δ 9.43 (s, 1H), 9.28
(s, 1H), 9.11 (dd, J = 1.5, 1.5 Hz, 1H), 8.57 (d, J = 9.0 Hz,
1H), 8.50 (t, J = 2.0 Hz, 1H), 8.48 (d, J = 2.0 Hz, 1H), 8.22 (d,
J = 8.5 Hz, 1H), 8.19 (d, J = 5.5 Hz, 1H), 7.95 (d, J = 7.5 Hz,
1H), 7.70 (d, J = 1.5 Hz, 1H), 7.64 (d, J = 4.5 Hz, 1H), 7.63-
7.61 (m, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.37 (dd, J = 2.0, 1.5
Hz, 1H); ESI-MS: m/z, 376 (M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(3,5-dichloro-
phenyl)urea (6g): Light brown solid;Yield: 50 %; m.p: 187-
189 °C; 1H NMR (500 MHz, DMSO-d6): δ 9.32 (s, 1H), 9.21
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(6-methyl-
pyrazin-2-yl)urea (6n): Light brown solid;Yield: 66 %; m.p:

774 Bhasker et al.
Asian J. Chem.
256-258 °C; 1H NMR (500 MHz, DMSO-d6): δ 9.86 (s, 1H),
9.59 (s, 1H), 9.12 (dd, J = 2.0, 2.0 Hz, 1H), 8.87 (s, 1H), 8.58
(d, J = 8.5 Hz, 1H), 8.52-8.49 (m, 2H), 8.24 (d, J = 8.5 Hz,
1H), 8.17 (s, 1H), 7.97-7.95 (m, 1H), 7.66-7.64 (m, 1H), 7.63
(d, J = 4.0 Hz, 1H), 7.54 (t, J = 8.0 Hz, 1H), 2.46 (s, 3H); ESI-
MS: m/z, 357.09 (M+1).
strains viz., Escherichia coli, Klebsiella pneumonia, Staphylo-
coccus aureus and Bacillus subtilis. The results are summarized
in Table-1 and ampicilline was used as positive control. It is
observed that compounds 6g, 6h and 6p revealed excellent
antibacterial activity with zone of inhibition 30-33 mm against
Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus
and Bacillus subtilis, while compounds 6g, 6h and 6p displayed
excellent antibacterial activity with zone of inhibition 9-12
mm.
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(m-tolyl)urea
1
(6o): Light brown solid; Yield: 70 %; m.p: 207-211 °C; H
NMR (500 MHz, DMSO-d6): δ 9.11 (dd, J = 4.0, 2.0 Hz, 1H),
8.94 (brs, 1H), 8.64 (brs, 1H), 8.57 (d, J = 8.5 Hz, 1H), 8.50
(t, J = 2.0 Hz, 1H), 8.48 (d, J = 1.5 Hz, 1H), 8.21 (d, J = 8.5 Hz,
1H), 7.89 (d, J = 8.0 Hz, 1H), 7.64-7.59 (m, 1H), 7.48 (t, J = 7.5
Hz, 1H), 7.36 (brs, 1H), 7.29-7.25 (m, 1H), 7.22-7.13 (m, 2H),
6.81-6.77 (m, 1H), 2.27 (s, 3H); ESI-MS: m/z, 355 (M+1).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(3-chloro-4-
cyanophenyl)urea (6p): Light brown solid;Yield: 55 %; m.p:
230-235 °C; 1H NMR (500 MHz, DMSO-d6): δ 9.47 (s, 1H),
9.28 (s, 1H), 9.12 (dd, J = 1.5, 1.5 Hz, 1H), 8.59 (d, J = 8.5
Hz, 1H), 8.52 (q, J = 3.0, 1.5 Hz, 1H), 8.51 (d, J = 2.0 Hz,
1H), 8.24 (d, J = 8.5 Hz, 1H), 8.01 (d, J = 2.0 Hz, 1H), 7.95-
7.93 (m, 1H), 7.86 (d, J = 9.0 Hz, 1H), 7.66-7.64 (m, 1H),
7.62 (d, J = 1.5 Hz, 1H), 7.55-7.52 (m, 1H), 7.50 (d, J = 2.0
Hz, 1H); ESI-MS: m/z, 400 (M+1).
REFERENCES
1. D. Bouzard, Recent Progress in the Chemical Synthesis of Antibiotics:
Recent Advances in the Chemistry of Quinolines, Springer Verlag,
Berlin. pp. 249 (1990).
2. C. Siporin, C.L. Heifetz and J.M. Domagala, The New Generation of
Quinolines, M. Dekker, New York (1990).
3. P.A. Lowe, Naphthyridines, Pyridoquinolines,Anthyridines and Similar
Compounds, Comprehensive Heterocyclic Chemistry, vol. II, pp. 581-
627 (1984).
4. A.S. Tomcufcik, W.E. Meyer and J.W. Marisco, Eur. Pat. Appl. EP
446604 (1991).
5. E.V. Brown, R.M. Novack and A.A. Hamdan, J. Org. Chem., 26, 2831
(1961);
https://doi.org/10.1021/jo01066a050.
6. E.V. Brown, R.M. Novack and A.A. Hamdan, J. Natl. Cancer Inst., 26,
1461 (1961).
1-[3-(1,8-Naphthyridin-2-yl)phenyl]-3-(5-methyl-[1,1'-
biphenyl]-3-yl)urea (6q): Light brown solid; Yield: 62 %;
m.p: 230-235 °C; 1H NMR (500 MHz, DMSO-d6): δ 9.11 (s,
1H), 8.99 (s, 1H), 8.75 (s, 1H), 8.57 (d, J = 8.0 Hz, 1H), 8.53
(s, 1H), 8.50 (d, J = 7.5 Hz, 1H), 8.22 (d, J = 8.5 Hz, 1H), 7.90
(d, J = 7.5 Hz, 1H), 7.64-7.60 (m, 5H), 7.51-7.46 (m, 3H),
7.37 (t, J = 7.5 Hz, 1H), 7.31 (s, 1H), 7.10 (s, 1H), 2.37 (s,
3H); ESI-MS: m/z, 431 (M+1).
7. H. Egawa, T. Miyamoto, A. Minamida,Y. Nishimura, H. Okada, H. Uno
and J. Matsumoto, J. Med. Chem., 27, 1543 (1984);
https://doi.org/10.1021/jm00378a004.
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11. R. Peters and I.G. Young, The Chemistry of Steroids, Wilmer Brother
and Harman Ltd, Birkenhead, p. 112 (1960).
RESULTS AND DISCUSSION
12. N. Suzuki, Pharm. Bull., 28, 761 (1980);
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https://doi.org/10.1071/CH9841065.
Antibacterial activity: All the synthesized compounds
(6a-q) were evaluated for their antibacterial activity against
two Gram-negative and two Gram-positive bacterial strains
15. R.S. Lodhi and S.D. Srivastsava, Indian J. Chem., 36B, 947 (1997).
16. S.S. Shankar, E. Laxminarayana, B. Srinivasulu and M.T. Chary, Indian
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17. E. Laxminarayana, A. Narender, S.S. Shankar and M.T. Chary, Int. J.
Appl. Chem., 4, 237 (2008).
TABLE-1
ANTIMICROBIAL ACTIVITY (ZONE OF INHIBITION)
OF NOVEL 1-[3-(1,8-NAPHTHYRIDIN-2-YL)PHENYL]-
3-ARYLUREA DERIVATIVES (conc. 20 µg/10 µL)
Compd.
No.
Escherichia Staphylococcus Klebsiella Bacillus
18. M.T. Chary, E. Laxminarayana, S.S. Shankar andA. Narender, Hetercycl.
Commun., 15, 35 (2009);
coli
aureus
pneumonia subtilis
https://doi.org/10.1515/HC.2009.15.1.35.
19. A. Narender, M.T. Chary, E. Laxminarayana and V. Haripriya, Indian
J. Chem., 52B, 440 (2013).
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54, 289 (2009);
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21. A. Narender, E. Laxminarayana, S.S. Shankar and M.T. Chary, Hetercycl.
Commun., 16, 187 (2010);
https://doi.org/10.1515/HC.2010.16.2-3.187.
22. A. Narendar, E. Laxminarayana and M.T. Chary, Indian J. Heterocycl.
Chem., 23, 239 (2014).
23. K.K. Anantoju, G. Tharikoppula, L. Eppakayala and T.C. Maringanti,
Int. J. Chem. Anal. Sci., 4, 146 (2013);
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
2
2
1
3
8
2
11
12
2
2
8
5
9
3
2
10
3
13
1
1
1
6
7
5
9
4
5
3
6
4
8
2
5
9
2
15
1
1
2
3
2
0
4
3
3
3
5
5
8
0
2
7
2
14
1
1
1
4
6
3
0
3
3
0
4
2
9
0
0
7
0
13
https://doi.org/10.1016/j.ijcas.2013.07.008.
24. M. Bucha, L. Eppakayala, T.C. Maringanti, G. Tharikoppula and S.
Kethireddy, Org. Med. Chem. Lett., 4, 16 (2014);
https://doi.org/10.1186/s13588-014-0016-8.
Ampllicin